Synthesis of 7-epineoptilocaulin, mirabilin B, and isoptilocaulin. A unified biosynthetic proposal for the ptilocaulin and batzelladine alkaloids. Synthesis and structure revision of netamines E and G.
Addition of guanidine to a 6-methylhexahydroindenone in MeOH at 85 degrees C afforded 7-epineoptilocaulin. A similar reaction with a 6-propylhexahydroindenone afforded netamine E. MnO2 oxidation of 7-epineoptilocaulin and netamine E afforded mirabilin B and netamine G, respectively. The netamines have the side chains trans, not cis as was initially proposed. A unified biosynthetic scheme for the batzelladines and ptilocaulin family is proposed. Conjugate addition of guanidine to a bis enone followed by an intramolecular Michael reaction of the enolate to the other enone, aldol reaction, dehydration, and enamine formation will lead to a tricyclic intermediate at the dehydroptilocaulin oxidation state. 1,4-Hydride addition will lead to ptilocaulin or 7-epineoptilocaulin depending on which face the hydride adds to. 1,2-Hydride addition will lead to isoptilocaulin. The key tricyclic intermediate was prepared from a tetrahydroindenone and guanidine and reduced with NaBH4 to give a mixture rich in ptilocaulin and isoptilocaulin.
Yu
Min
M
Department of Chemistry MS 015, Brandeis University, Waltham, Massachusetts 02454-9110, USA.
Pochapsky
Susan S
SS
Snider
Barry B
BB
D000470:Alkaloids / Q000096:biosynthesis*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D012503:Saponins / Q000138:chemical synthesis*; D013237:Stereoisomerism
C534162:7-epineoptilocaulin; D000470:Alkaloids; D011799:Quinazolines; D012503:Saponins; C105644:mirabilin; C534163:netamine E; C534164:netamine G; D009828:Oleanolic Acid; C061200:ptilocaulin